Anti-CEA tagged iron nanoparticles for targeting triple-negative breast cancer.

Systemic therapy is generally required for breast cancer. However, treatment toxicity and side effects are a concern, especially for triple-negative breast cancer (TNBC), a subtype that usually develops resistance to chemotherapy. To overcome this issue, new nanoformulations capable of targeting cancer cells have been developed and alternative biomarkers have been explored as target molecules for TNBC management. In this study, we performed anin vivoassay in a murine orthotopic TNBC model to evaluate the targeting ability of anti-carcinoembryonic antigen (anti-CEA) loaded nanoparticles (labelled MFCEA), which had been previously synthetized by our research group. 4T1 cells were injected in the mammary gland of balb-c mice, and tumors were evaluated for CEA expression by immunohistochemistry. Tumor-bearing mice received targeted (MFCEA) and non-targeted (MF) nanoparticles intraperitoneally. Tumors were removed 1, 4, 15 and 24 h after treatment, and Prussian blue iron staining was performed. Our results showed, as far as we know for the first time, that 4T1 induced tumors are CEA positive, and this opens up new prospects for treating TNBC. Furthermore, MFCEA nanoparticles were able to target malignant tissue and were retained in the tumor for longer than MF nanoparticles. The retention property of MFCEA, together with the absence of toxicity observed in the MTT assay, make these nanoparticles a promising device for management of CEA positive tumors and perhaps for TNBC. Nevertheless, further studies must be carried out to improve their performance and ensure safety for clinical studies.

Venomic and pharmacological activity of Acanthoscurria paulensis (Theraphosidae) spider venom.

In the present study we conducted proteomic and pharmacological characterizations of the venom extracted from the Brazilian tarantula Acanthoscurria paulensis, and evaluated the cardiotoxicity of its two main fractions. The molecular masses of the venom components were identified by mass spectrometry (MALDI-TOF-MS) after chromatographic separation (HPLC). The lethal dose (LD(50)) was determined in mice. Nociceptive behavior was evaluated by intradermal injection in mice and the edematogenic activity by the rat hind-paw assay. Cardiotoxic activity was evaluated on in situ frog heart and on isolated frog ventricle strip. From 60 chromatographic fractions, 97 distinct components were identified, with molecular masses between 601.4 and 21,932.3 Da. A trimodal molecular mass distribution was observed: 30% of the components within 500-1999 Da, 38% within 3500-5999 Da and 21% within 6500-7999 Da. The LD(50) in mice was 25.4 ± 2.4 µg/g and the effects observed were hypoactivity, anuria, constipation, dyspnea and prostration until death, which occurred at higher doses. Despite presenting a dose-dependent edematogenic activity in the rat hind-paw assay, the venom had no nociceptive activity in mice. Additionally, the venom induced a rapid blockage of electrical activity and subsequent diastolic arrest on in situ frog heart preparation, which was inhibited by pretreatment with atropine. In the electrically driven frog ventricle strip, the whole venom and its low molecular mass fraction, but not the proteic one, induced a negative inotropic effect that was also inhibited by atropine. These results suggest that despite low toxicity, A. paulensis venom can induce severe physiological disturbances in mice.

Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells.

Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

Bracken-fern extracts can be clastogenic or aneugenic depending on the tissue cell assay.

The consumption of bracken fern (Pteridium aquilinum) as food is associated with a high incidence of cancer in humans and animals. We investigated the cytogenetic effects of bracken-fern extracts (hexane extract-HE, ethanol extract-EE, hot water extract-HWE and cold water extract-CWE) on chromosomes of peritoneal and bone-marrow cells of Swiss mice. In peritoneal cells, all four treatments (HE, EE, HWE and CWE) induced structural chromosome aberrations, but the EE also induced numerical chromosome aberrations. In bone-marrow cells both HE and CWE induced structural chromosome aberrations; additionally, the number of abnormal metaphases was higher in peritoneum than in bone marrow. We suggest that bracken fern induces cytogenetic damage through DNA strand breaks and affects chromosome segregation.